rs4627412

Variant names:

• chr17-80550444-G-A
• rs4627412
• NM_020761.3:c.162+4653G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.162+4653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,026 control chromosomes in the GnomAD database, including 29,814 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29814 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 6 publications found

Genes affected

RPTOR (HGNC:30287): (regulatory associated protein of MTOR complex 1) This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.162+4653G>A		intron_variant	Intron 1 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.162+4653G>A		intron_variant	Intron 1 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+4653G>A		intron_variant	Intron 1 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93927 AN: 151908 Hom.: 29818 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.657

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 93940 AN: 152026 Hom.: 29814 Cov.: 32 AF XY: 0.613 AC XY: 45510 AN XY: 74298

African (AFR) AF: 0.502 AC: 20806 AN: 41450

American (AMR) AF: 0.540 AC: 8245 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2582 AN: 3470

East Asian (EAS) AF: 0.582 AC: 3010 AN: 5168

South Asian (SAS) AF: 0.526 AC: 2539 AN: 4824

European-Finnish (FIN) AF: 0.635 AC: 6706 AN: 10566

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47875 AN: 67976

Other (OTH) AF: 0.653 AC: 1375 AN: 2106

Alfa AF: 0.673 Hom.: 17311

Bravo AF: 0.607

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4627412; hg19: chr17-78524244;